Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets

Abstract

Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases. Nonetheless, despite notable progress, the exploration of the relationship between programmed cell death and disease, as well as its clinical application, are still in a nascent stage. Therefore, further exploration of programmed cell death and the development of corresponding therapeutic methods and strategies holds substantial potential. Our review provides a detailed examination of the primary mechanisms behind apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Following this, the discussion delves into biological functions and diseases associated dysregulated programmed cell death. Finally, we highlight existing and potential therapeutic targets and strategies focused on cancers and neurodegenerative diseases. This review aims to summarize the latest insights on programmed cell death from mechanisms to diseases and provides a more reliable approach for clinical transformation.

Abstract

Programmed cell death is a type of autonomic and orderly cell death mode controlled by genes. We reviewed molecular mechanisms of five programmed cell death, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. Programmed cell death is widely involved in the normal physiological process of the organism. We described the normal biological functions of programmed cell death from four perspectives like development and tissue homeostasis, immune regulation, response to cellular stress, and elimination of damaged or infected cells. Conversely, dysregulated PCD is implicated in the occurrence and progression of numerous diseases. Relevant progressions of programmed cell death observed in cancer, neurodegenerative diseases, and autoimmune disorders were summarized. Based on these, key proteins in each pathway thus become important regulatory targets. PCD‐based therapies, including small molecule drugs, cannot be ignored.